Real-time analysis of dopamine: antagonist interactions at recombinant human D2long receptor upon modulation of its activation state.

Abstract:

:1. Antipsychotic drugs may mediate their therapeutic effects not only by preventing the binding of dopamine but also by decreasing the propensity of the dopamine receptor to assume an active R* state. Ligand-mediated activation and blockade of the recombinant human D(2long) receptor was investigated in CHO-K1 cells upon modulation of its R* state. 2. Both the Ala(371)Lys (A371K) and Thr(372)Arg (T372R) D2long receptor mutants could be activated in a ligand-dependent manner via a chimeric G(alphaq/o) protein, and more efficaciously so than with the promiscuous G(alpha15) protein. 3. Dopamine and partial agonists (E(max): lisuride > (+)-UH 232 approximately bromerguride) displayed dissimilar Ca(2+) kinetic properties at wild-type and mutant receptors. A371K and T372R D2long receptor mutants demonstrated an attenuated and enhanced maximal response to these partial agonists, respectively. 4. Dopamine antagonists were unable to block the transient high-magnitude Ca(2+) phase at the wild-type D2long receptor upon simultaneous exposure to antagonist and dopamine, while full blockade of the low-magnitude Ca(2+) phase did occur at a later time (onset-time: haloperidol < bromerguride < (+)-butaclamol). A similar, though more efficacious, antagonist profile was also found at the A371K mutant receptor. Conversely, the blockade of the low-magnitude Ca(2+) phase was attenuated (haloperidol) or almost absent [(+)-butaclamol and bromerguride] at the T372R mutant receptor. 5. In conclusion, mutagenesis of the Ala(371) and Thr(372) positions affects in an opposite way the ligand-dependent activation and blockade of the D2long receptor. The observed attenuation of dopamine-mediated Ca(2+) signal generation with different decay-times may underlie distinct properties of the dopaminergic ligands.

journal_name

Br J Pharmacol

authors

Pauwels PJ,Tardif S,Wurch T,Colpaert FC

doi

10.1038/sj.bjp.0704243

subject

Has Abstract

pub_date

2001-09-01 00:00:00

pages

88-97

issue

1

eissn

0007-1188

issn

1476-5381

journal_volume

134

pub_type

杂志文章
  • Vascular responses to 8-nitro-cyclic GMP in non-diabetic and diabetic mice.

    abstract:BACKGROUND AND PURPOSE:8-Nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP), formed nitric oxide (NO)-dependently, is a physiological second messenger, yet little is known about its role in the pathophysiology of vascular diseases. To study the pharmacological activity of 8-nitro-cGMP in diabetic mice, we compare...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.2011.01201.x

    authors: Tokutomi Y,Kataoka K,Yamamoto E,Nakamura T,Fukuda M,Nako H,Toyama K,Dong YF,Ahmed KA,Sawa T,Akaike T,Kim-Mitsuyama S

    更新日期:2011-04-01 00:00:00

  • Leptin potentiates IFN-gamma-induced expression of nitric oxide synthase and cyclo-oxygenase-2 in murine macrophage J774A.1.

    abstract::1. Leptin, a pleiotropic hormone believed to regulate body weight, has recently been associated with inflammatory states and immune activity. Here we have studied the effect of leptin on expression of IFN-gamma-induced nitric oxide synthase (iNOS) and cyclo-oxygenase-2 (COX-2), both prominent markers of macrophage act...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0704903

    authors: Raso GM,Pacilio M,Esposito E,Coppola A,Di Carlo R,Meli R

    更新日期:2002-11-01 00:00:00

  • Antianxiety and antidepressant-like effects of AC-5216, a novel mitochondrial benzodiazepine receptor ligand.

    abstract::We investigated the ability of N-benzyl-N-ethyl-2-(7,8-dihydro-7-methyl-8-oxo-2-phenyl-9H-purin-9-yl)acetamide (AC-5216), a novel mitochondrial benzodiazepine receptor (MBR) ligand, to produce anti-anxiety and antidepressant-like effects in various animal models. AC-5216 showed high affinity for MBRs prepared from rat...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0705681

    authors: Kita A,Kohayakawa H,Kinoshita T,Ochi Y,Nakamichi K,Kurumiya S,Furukawa K,Oka M

    更新日期:2004-08-01 00:00:00

  • Effects of hypoxia on the pharmacological responsiveness of isolated coronary artery rings from the sheep.

    abstract::1. The effects of low oxygen tension on tone and on the responsiveness to contractile and relaxant agents were examined on circumflex coronary artery rings isolated from sheep. 2. When artery rings (2-2.5 mm o.d.) were set at their optimal resting tension, introduction of hypoxia (0% O2) caused a sustained contraction...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1989.tb11894.x

    authors: Kwan YW,Wadsworth RM,Kane KA

    更新日期:1989-04-01 00:00:00

  • Further studies on the mode of action of psychotomimetic drugs: antagonism of the excitatory actions of 5-hydroxytryptamine by methylated derivatives of tryptamine.

    abstract::1 The actions of 5-methoxytryptamine (5-MeOT), N,N-dimethyltryptamine (DMT), 5-hydroxy-N,N-dimethyltryptamine (bufotenine, 5-HODMT) and 5-methoxy-N,N-dimethyltryptamine (5-MeODMT), and their interactions with 5-hydroxytryptamine (5-HT), acetylcholine, (-)-noradrenaline, and glutamate were studied by microiontophoresis...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1974.tb09609.x

    authors: Bradley PB,Briggs I

    更新日期:1974-03-01 00:00:00

  • Delphinidin and cyanidin inhibit PDGF(AB)-induced VEGF release in vascular smooth muscle cells by preventing activation of p38 MAPK and JNK.

    abstract:BACKGROUND AND PURPOSE:Red wine polyphenols (RWPs) inhibit the expression of vascular endothelial growth factor (VEGF), a major pro-angiogenic and pro-atherosclerotic factor, in vascular smooth muscle cells (VSMCs). The aim of this study was to identify which red wine polyphenols were inhibitory and to determine the me...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0706843

    authors: Oak MH,Bedoui JE,Madeira SV,Chalupsky K,Schini-Kerth VB

    更新日期:2006-10-01 00:00:00

  • Presynaptic alpha-adrenoceptors: do exogenous and neuronally released noradrenaline act at different sites?

    abstract::The effects of dopamine receptor and alpha-adrenoceptor agonists and antagonists on the stimulation-evoked overflow of radioactivity from strips of dog saphenous vein previously loaded with [3H]-noradrenaline have been examined alone and in combination. In the presence of neuronal and extraneuronal catecholamine uptak...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1984.tb10098.x

    authors: Baker DJ,Drew GM,Hilditch A

    更新日期:1984-03-01 00:00:00

  • Modification of cardiovascular responses to histamine by dithiothreitol.

    abstract::1 Histamine produced dose-dependent contractile responses on both isolated perfused ear arteries and aortic strips of the rabbit. These responses were blocked by mepyramine and potentiated by both metiamide and dithiothreitol. 2 In the presence of maximum potentiation by metiamide, dithiothreitol still potentiated the...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1977.tb07497.x

    authors: Carroll PR,Glover WE

    更新日期:1977-02-01 00:00:00

  • Rho kinase inhibitor fasudil reduces l-DOPA-induced dyskinesia in a rat model of Parkinson's disease.

    abstract:BACKGROUND AND PURPOSE:Rho kinase (ROCK) activation is involved in neuroinflammatory processes leading to progression of neurodegenerative diseases such as Parkinson's disease. Furthermore, ROCK plays a major role in angiogenesis. Neuroinflammation and angiogenesis are mechanisms involved in developing l-DOPA-induced d...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/bph.15275

    authors: Lopez-Lopez A,Labandeira CM,Labandeira-Garcia JL,Muñoz A

    更新日期:2020-12-01 00:00:00

  • Characterization of the non-nitrergic NANC relaxation responses in the rabbit vaginal wall.

    abstract::Electrical field stimulation (EFS)-induced non-adrenergic non-cholinergic (NANC) relaxation responses in the rabbit vaginal wall were investigated. These NANC responses were partially inhibited with the nitric oxide synthase (NOS) inhibitors N(G)-nitro-L-arginine methyl ester (L-NAME; 500 microM), N(G)-nitro-L-arginin...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0704481

    authors: Ziessen T,Moncada S,Cellek S

    更新日期:2002-01-01 00:00:00

  • Effects of amino acids and convulsants on spontaneous action potentials in cerebellar cortex slices.

    abstract::1 Picrotoxin selectively and reversibly suppressed the inhibitory action of gamma-aminobutyric acid (GABA), but not that of glycine, taurine or beta-alanine, on the frequency of spontaneous spike discharges in guinea-pig cerebellar slices. Strychnine reversibly suppressed the inhibitory action of glycine, taurine or b...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1976.tb07650.x

    authors: Okamoto K,Quastel JH

    更新日期:1976-05-01 00:00:00

  • Binding of [3H]-muscimol, a potent gamma-aminobutyric acid receptor agonist, to membranes of the bovine retina.

    abstract::1 The binding of [3H]-muscimol, a potent gamma-aminobutyric acid (GABA) receptor agonist, to crude membrane preparations of bovine retina was studied, using a filtration method to isolate membrane-bound ligand. 2 Specific binding was found to be saturable and occurred at two binding sites with affinity constants of 4....

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1980.tb10934.x

    authors: Osborne NN

    更新日期:1980-01-01 00:00:00

  • Discovery, characterization and clinical utility of prostaglandin agonists for the treatment of glaucoma.

    abstract::Topical ophthalmic formulations of analogues of the endogenous arachidonic acid cyclooxygenase metabolite, PGF2α , are the standard of care treatment for the blinding disease glaucoma. These are the most potent and efficacious medical therapies for lowering intraocular pressure (IOP), the most important risk factor id...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章,评审

    doi:10.1111/bph.14327

    authors: Klimko PG,Sharif NA

    更新日期:2019-04-01 00:00:00

  • Effects of inhibitors of the activity of poly (ADP-ribose) synthetase on the organ injury and dysfunction caused by haemorrhagic shock.

    abstract::1 Poly (ADP-ribose) synthetase (PARS) is a nuclear enzyme activated by strand breaks in DNA, which are caused by reactive oxygen species (ROS). Here we investigate the effects of the PARS inhibitors 3-aminobenzamide (3-AB), nicotinamide and 1,5-dihydroxyisoquinoline (ISO) on the circulatory failure and the organ injur...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0702928

    authors: McDonald MC,Filipe HM,Thiemermann C

    更新日期:1999-11-01 00:00:00

  • Amlodipine, but not verapamil or nifedipine, dilates rabbit femoral artery largely through a nitric oxide- and kinin-dependent mechanism.

    abstract::1. We investigated the nitric oxide (NO) dependence of vasorelaxation in response to different calcium channel blockers (CCB), in rabbit femoral artery in vivo. 2. Anaesthetized rabbits underwent femoral artery ligation, and blood from the proximal artery was returned distal to the ligature through a constant infusion...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0704753

    authors: Xu B,Xiao-hong L,Lin G,Queen L,Ferro A

    更新日期:2002-06-01 00:00:00

  • Noradrenaline-induced relaxation of rat oesophageal muscularis mucosae: mediation solely by innervated beta 3-adrenoceptors.

    abstract::We investigated the effects of cocaine and corticosterone on the noradrenaline-induced relaxation of rat oesophageal smooth muscle in the absence and presence of the selective beta2-antagonist, ICI 111,551. It was found that the concentration-response curve (CRC) of noradrenaline was not shifted by ICI 118,551 at 1 mi...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1995.tb16396.x

    authors: de Boer RE,Brouwer F,Zaagsma J

    更新日期:1995-10-01 00:00:00

  • Temperature-sensitive transient receptor potential vanilloid channels: structural insights into ligand-dependent activation.

    abstract::Temperature-sensitive transient receptor potential vanilloid ion channel subtypes 1-4 (thermoTRPV1-thermoTRPV4) play important roles in a wide range of physiological processes, including temperature sensing and body temperature regulation, inflammation, pain, itch, maintenance of skin, bone and hair, along with osmoti...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章,评审

    doi:10.1111/bph.15310

    authors: Zubcevic L

    更新日期:2020-11-06 00:00:00

  • Characterization of the postjunctional alpha 2C-adrenoceptor mediating vasoconstriction to UK14304 in porcine pulmonary veins.

    abstract:BACKGROUND AND PURPOSE:In terms of postjunctional alpha(2)-adrenoceptors in the pulmonary circulation, no evidence is available with regard to the receptor subtypes mediating vasoconstriction. Therefore, we characterized the alpha(2)-adrenoceptor subtypes mediating contraction in isolated porcine pulmonary veins. EXPE...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0707221

    authors: Görnemann T,von Wenckstern H,Kleuser B,Villalón CM,Centurión D,Jähnichen S,Pertz HH

    更新日期:2007-05-01 00:00:00

  • Modification by drugs of the secretagogue effect of dopamine on the pancrease.

    abstract::1 The specific stimulating action of dopamine and L-DOPA on exocrine pancreatic secretion was further investigated in the isolated blood-perfused canine pancreas.2 6-Hydroxydopamine (100 mug, i.a.) stimulated the secretion but was far less potent than dopamine. Epinine (0.3-1 mg. i.a.), alpha-methyldopamine (10-300 mu...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1974.tb09651.x

    authors: Furuta Y,Hashimoto K,Ishii Y,Iwatsuki K

    更新日期:1974-06-01 00:00:00

  • An excitatory action of iontophoretically administered lithium on mammalian central neurones.

    abstract::1 The action of iontophoretically administered lithium was studied on spinal Renshaw cells an interneurones and on supraspinal neurones in cerebral cortex, thalamus, hypothalamus and brain stem in anaesthetized cats and rats. 2 There was a correlation between the effects of Li+ and those of acetylcholine (ACh), althou...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1977.tb07740.x

    authors: Haas HL,Ryall RW

    更新日期:1977-06-01 00:00:00

  • An autoradiographic study of dextromethorphan high-affinity binding sites in rat brain: sodium-dependency and colocalization with paroxetine.

    abstract::1. The distribution and some pharmacological properties of centrally located dextromethorphan high-affinity binding sites were investigated by in vitro autoradiography. 2. Sodium chloride (50 mM) induced a 7 to 12 fold increase in dextromethorphan binding to rat brain in all areas tested. The effect of sodium was conc...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0701043

    authors: Meoni P,Tortella FC,Bowery NG

    更新日期:1997-04-01 00:00:00

  • Cyclo-oxygenase isozymes in mucosal ulcergenic and functional responses following barrier disruption in rat stomachs.

    abstract::1. We examined the effects of selective and nonselective cyclo-oxygenase (COX) inhibitors on various functional changes in the rat stomach induced by topical application of taurocholate (TC) and investigated the preferential role of COX isozymes in these responses. 2. Rat stomachs mounted in ex vivo chambers were perf...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0701399

    authors: Hirata T,Ukawa H,Yamakuni H,Kato S,Takeuchi K

    更新日期:1997-10-01 00:00:00

  • Screening for liver X receptor modulators: Where are we and for what use?

    abstract::Liver X receptors (LXRs) are members of the nuclear receptor superfamily that are canonically activated by oxidized derivatives of cholesterol. Since the mid-90s, numerous groups have identified LXRs as endocrine receptors that are involved in the regulation of various physiological functions. As a result, when their ...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章,评审

    doi:10.1111/bph.15286

    authors: Buñay J,Fouache A,Trousson A,de Joussineau C,Bouchareb E,Zhu Z,Kocer A,Morel L,Baron S,Lobaccaro JA

    更新日期:2020-10-20 00:00:00

  • Cytokine induction of NO synthase II in human DLD-1 cells: roles of the JAK-STAT, AP-1 and NF-kappaB-signaling pathways.

    abstract::1. In human epithelial-like DLD-I cells, nitric oxide synthase (NOS) II expression was induced by interferon-gamma (100 u ml(-1)) alone and, to a larger extent, by a cytokine mixture (CM) consisting of interferon-gamma, interleukin-1beta (50 u ml(-1)) and tumor necrosis factor-alpha (10 ng ml(-1)). 2. CM-induced NOS I...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0702039

    authors: Kleinert H,Wallerath T,Fritz G,Ihrig-Biedert I,Rodriguez-Pascual F,Geller DA,Förstermann U

    更新日期:1998-09-01 00:00:00

  • Characterization of the binding of DL-[3H]-2-amino-4-phosphonobutyrate to L-glutamate-sensitive sites on rat brain synaptic membranes.

    abstract::The binding of DL-[3,4-3H] 2-amino-4-phosphonobutyric acid DL[3H]-APB to rat whole brain synaptic membranes was investigated. Binding was linear with membrane protein concentration, and optimal at physiological pH and temperature. The association rate was rapid, achieving equilibrium within 10 min. Prolonged incubatio...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1983.tb10041.x

    authors: Butcher SP,Collins JF,Roberts PJ

    更新日期:1983-10-01 00:00:00

  • alpha-Adrenoceptor-mediated depletion of phosphatidylinositol 4, 5-bisphosphate inhibits activation of volume-regulated anion channels in mouse ventricular myocytes.

    abstract:BACKGROUND AND PURPOSE:Volume-regulated anion channels (VRACs) play an important role in cell-volume regulation. alpha(1)-Adrenoceptor stimulation by phenylephrine (PE) suppressed the hypotonic activation of VRAC current in mouse ventricular cells and regulatory volume decrease (RVD) was also absent in PE-treated cells...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.2010.00896.x

    authors: Ichishima K,Yamamoto S,Iwamoto T,Ehara T

    更新日期:2010-09-01 00:00:00

  • Investigation of the effects of 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB) on membrane currents in rat portal vein.

    abstract::1. The effects of 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB) were investigated on evoked and spontaneous currents in freshly-isolated cells from the rat portal vein by use of conventional whole-cell recording and perforated-patch techniques. 2. At a holding potential of -60 mV in potassium-free, caesium-conta...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1996.tb15171.x

    authors: Kirkup AJ,Edwards G,Weston AH

    更新日期:1996-01-01 00:00:00

  • Ryanodine reveals multiple contractile and relaxant mechanisms in vascular smooth muscle: simultaneous measurements of mechanical activity and of cytoplasmic free Ca2+ level with fura-2.

    abstract::1. The effects of ryanodine on changes in cytoplasmic Ca2+ level ([Ca2+]i) and muscle tension induced by maximum concentrations of phenylephrine (Phe; 1 microM), prostaglandin F2 alpha (PGF2 alpha, 10 microM), caffeine (Caf, 30 mM) and isoprenaline (Iso, 1 microM) were examined in rat aortic strips using fura-2. 2. In...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1990.tb14075.x

    authors: Hisayama T,Takayanagi I,Okamoto Y

    更新日期:1990-08-01 00:00:00

  • Absence of P2-purinoceptors in hippocampal pathways.

    abstract::1. Many apparent actions of adenosine 5'-triphosphate (ATP) are mediated by adenosine produced by enzymatic hydrolysis of the nucleotide. Previously described actions of ATP in the CNS have been partly due to this phenomenon. In the present study analogues of ATP, which are not hydrolysed to adenosine, were used to se...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1989.tb11996.x

    authors: Stone TW,Cusack NJ

    更新日期:1989-06-01 00:00:00

  • Validation of IKK beta as therapeutic target in airway inflammatory disease by adenoviral-mediated delivery of dominant-negative IKK beta to pulmonary epithelial cells.

    abstract::Asthma is an inflammatory disease of the lungs and the transcription factor NF-kappa B regulates the production of numerous inflammatory mediators that may have a role in the pathogenesis of asthma. Hence, the signalling pathways leading to NF-kappa B activation are considered prime targets for novel anti-inflammatory...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0706170

    authors: Catley MC,Chivers JE,Holden NS,Barnes PJ,Newton R

    更新日期:2005-05-01 00:00:00